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Biomedical subjects

G Mark

Publications and source records attributed to G Mark.

At least 19 recordsLinked to original sources
PubMed2003

Differentiation of parkinsonian syndromes according to differences in executive functions.

Groups of patients with Parkinson's disease (PD), striatonigral degeneration-type multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) with motor disability stages II and III according to Hoehn and Yahr, and a healthy control group were compared using neuropsychological tests of executive functions. The results indicate that all three patient groups were impaired in the tests of executive functions. In comparison with healthy subjects, the three patient groups showed impaired performance regarding verbal fluency, problem solving and verbal and figural working memory. Patients with PD differed significantly from healthy subjects in a test of verbal recency, while patients with MSA or PSP were unimpaired. The comparison of patient groups revealed no differences between PD and MSA patients. However, patients with PSP showed greater impairment in both phonemic and semantic fluency than patients with PD or MSA. Using discriminant function analysis, it was found that variables derived from four verbal fluency tasks (simple and alternate semantic and phonemic fluency) discriminated among the three patient groups at a level significantly exceeding chance. Over 90% of patients with PSP were correctly classified. Patients with PD and MSA were correctly classified in over 70% of cases. These results suggest that verbal fluency tasks may be sensitive measures in the differential diagnosis of PD, MSA and PSP.

Aged↗
PubMed2001

[Anterior interosseous nerve syndrome as differential diagnosis of closed isolated flexor tendon lesion].

Lesions of the anterior interosseus nerve can result in a variety of clinical manifestations, depending on location and degree of axonal damage. Clinical presentation with an isolated palsy of the flexor pollicis longus muscle is difficult to distinguish from a closed tendon rupture, especially when a trauma occurred. We would like to present five of our cases and discuss the diagnostic and therapeutic modalities.

Adult↗
PubMed2001

Far-field responses to stimulation of the cochlear nucleus by microsurgically placed penetrating and surface electrodes in the cat.

OBJECT: A new generation of penetrating electrodes for auditory brainstem implants is on the verge of being introduced into clinical practice. This study was designed to compare electrically evoked auditory brainstem responses (EABRs) to stimulation of the cochlear nucleus (CN) by microsurgically implanted surface electrodes and insertion electrodes (INSELs) with stimulation areas of identical size. METHODS: Via a lateral suboccipital approach, arrays of surface and penetrating microelectrodes with geometric stimulation areas measuring 4,417 microm2 (diameter 75 microm) were placed over and inserted into the CN in 10 adult cats. After recording the auditory brainstem response (ABR) at the mastoid process, the CN, and the level of the inferior colliculus, EABRs to stimulation of the CN were recorded using biphasic, charge-balanced stimuli with phase durations of 80 microsec, 160 microsec, and 240 microsec at a repetition rate of 22.3 Hz. Waveform, threshold, maximum amplitude, and the dynamic range of the responses were compared for surface and penetrating electrodes. The EABR waveforms that appeared for both types of stimulation resembled each other closely. The mean impedance was slightly lower (30 +/- 3.4 kohm compared with 31.7 +/- 4.5 kohm, at 10 kHz), but the mean EABR threshold was significantly higher (51.8 microA compared with 40.5 microA, t = 3.5, p = 0.002) for surface electrode arrays as opposed to penetrating electrode arrays. Due to lower saturation levels of the INSEL array, dynamic ranges were almost identical between the two types of stimulation. Sectioning of the eighth cranial nerve did not abolish EABRs. CONCLUSIONS: Microsurgical insertion of electrodes into the CN complex may be guided and monitored using techniques similar to those applied for implantation of surface electrodes. Lower thresholds and almost equivalent dynamic ranges indicate that a more direct access to secondary auditory neurons is achieved using penetrating electrodes.

Animals↗
PubMed2001

Induction of mammary epithelial cell differentiation and inhibition of dimethylbenz(A)anthracene-induced mammary tumour by co-administration of a pure antiestrogen ICI 182,780 and testosterone enanthate.

Epidemiological studies have shown that early first pregnancy is associated with a life-long reduction in breast cancer risk. The terminal differentiation associated with pregnancy and lactation has been proposed as a mechanism underlying the protective effect of pregnancy. We report that treatment of rats with ICI 182,780 (ICI) caused a marked reduction in epithelial cells and Ki-67 labelling index as compared to controls and testosterone enanthate-treated (TE) mammary glands. TE increased the Ki-67 labelling index, stimulated lobuloalveolar and ductal growth, as well as the secretory activity of acinar cells. Co-administration of TE and ICI resulted in a reduction in Ki-67 labelling index. Mammary epithelial cells became differentiated, resembling that observed at the end of pregnancy and during lactation as indicated by marked increase in secretory activity, lipid accumulation and presence of basal nuclei. The expression of differentiation markers such as whey acidic protein, mammary derived growth inhibitor, alpha-casein and beta-casein was detected only in TE plus ICI treated mammary tissues. Unlike TE, ICI caused a significant reduction in DMBA-induced tumour incidence, number of tumour bearing and tumour size. Tumour incidence was reduced to 8% when both ICI and TE were co-administered. Our data provide the novel molecular interactions between the estrogen and androgen in regulation of mammary growth and differentiation. These observations may give insight into novel actions of ICI and TE on breast differentiation and protection against carcinogenesis which may be useful in designing novel strategies for cancer prevention and/or treatment based on maximizing mammary epithelial cell differentiation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Workshop IV: drug treatment guidelines for the long-term management of Parkinson's disease.

An attempt was made to establish a decision algorithm for the treatment of idiopathic Parkinson's disease at various stages and in different subgroups such as akinetic-rigid or tremor dominance type. We suggest treating young patients with selegiline and a dopamine agonist. In the tremor dominance type we use either budipine or a dopamine agonist. Due to levodopa-induced dyskinesia, we try to avoid levodopa in the early stages of the disease and use it only later in more advanced situations in a combination therapy with dopamine agonists. Since IPS is not only based upon dopamine deficiency but also on resulting glutamatergic overstimulation, we advocate the use of a glutamate antagonist such as amantadine or budipine. Catechol-O-methyl inhibitors are very helpful when wearing-off occurs. Anticholinergics are only used in the early stages of tremor-dominant IPS because we fear enhancing the risk of dementia.

Adult↗
PubMed1999

Epitope insertion into variable loops of HIV-1 gp120 as a potential means to improve immunogenicity of viral envelope protein.

We report on the properties of a set of HIV-1 IIIB Env mutants carrying a linear gp41 epitope insertion (LLELDKWASL) in the V1, V2, V3 or V4 variable loop. Insertion of the epitope, which is defined by the HIV-1 neutralizing MAb 2F5, was well tolerated in the V1, V2 and V4 loops, as these mutants were properly expressed, retained reactivity to conformation-dependent monoclonal antibodies and exhibited patterns similar to the parental Env molecule. However, insertion of this epitope in the V3 loop was associated with drastically reduced protein expression. Relative to parental Env molecule, the V1, V2 and V4 insertion mutants demonstrated significantly increased binding to mAb 2F5 in vitro. To evaluate immunogenicity, mice and guinea pigs were immunized with plasmid expression vectors for the mutant proteins. For both mice and guinea pigs, all four mutants elicited anti-gp120 antibody responses. In mice the V1 and V3 insertion mutants, but neither the V2 or V4 insertion mutant nor the parental env, elicited significant titers against the epitope peptide, whereas in guinea pigs, V2 insertion mutant was most effective in eliciting anti-2F5 peptide antibody responses. While original V2 2F5 insertion mutant failed to elicit anti-2F5 peptide responses in mice, studies with 14 additional V2 insertion mutants revealed several insertion sites at which the epitope was able to induce epitope-specific antibody responses. This indicates that the precise position at which the epitope insertion takes place dictates the ability of the mutant to induce the epitope-specific antibody responses. When tested for virus neutralization activity, the guinea pig sera that contain high titers of anti-2F5 peptide antibody failed to enhance the virus neutralizing activity, suggesting that the configuration of 2F5 epitope plays a critical role in inducing neutralizing antibody responses. The results from this study may have potential implications with respect to modification of the HIV-1 Env molecule for the purpose of improving HIV-1 Env immunogenicity.

AIDS Vaccines↗
PubMed1998

Effects of c-raf-1 and c-myc expression on radiation response in an in vitro model of human small-cell-lung carcinoma.

In this study we examined the radiation survival response of simian virus 40 large tumor antigen-immortalized human bronchial epithelial cells (BEAS-2B) stably transfected with c-raf-1 and/or c-myc. C-raf-1 transfectants (2B-raf), and c-raf-1 and c-myc double transfectants (2B-raf/myc) were relatively radioresistant compared with c-myc (2B-myc) or control vector transfectants (2B-neo) (2B-raf, D0 = 2.445 Gy; 2B-raf/myc, D0 = 2.46 Gy; 2B-myc, D0 = 1.501 Gy; 2B-neo, D0 = 2.029 Gy). The steady state level of superoxide dismutase (SOD) mRNA was higher in radioresistant cells (2B-raf and 2B-raf/myc). In addition, 2B-raf but not 2B-raf/myc or 2B-myc transfectants revealed relatively higher number of cells in G2+M phase of the cell cycle. These findings present experimental evidence that Raf-1 expression correlates with the radiation-resistant response of 2B-raf or 2B-raf/myc transfectants and suggest a role of SOD in Raf-1-associated radiation resistance. Because 2B-raf transfectants are non-tumorigenic, and double transfectants (2B-raf/myc) are tumorigenic with some phenotypic traits found in small-cell lung carcinomas, our data imply a dissociation between the Raf-1-mediated mechanisms of radiation protection and progression of lung neoplasia.

Carcinoma, Small Cell↗
PubMed1998

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure. The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation. Sixty patients with chronic end-stage liver disease were included in a prospective randomized placebo-controlled study. NAC or the same volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Postoperative graft function was assessed by measurements of aminotransferases, prothrombin time, and monoethylglycinexylidide test over the 3 first postoperative days. Patient demographics were similar before the infusion of NAC or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen extraction ratio, and lactates were not different throughout the procedure. One hour after the revascularization of the hepatic artery, the oxygen extraction ratio by the liver was similar (17% +/- 7.6% v 17% +/- 6.2%) in both groups. Postoperative graft function was comparable within the 3 first postoperative days. This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease.

Acetylcysteine↗
PubMed1998

OH-radical formation by ultrasound in aqueous solution--Part II: Terephthalate and Fricke dosimetry and the influence of various conditions on the sonolytic yield.

Terephthalate and Fricke dosimetry have been carried out to determine the sonolytic energy yields of the OH free radical and of its recombination product H2O2 in aqueous solutions under various operating conditions (nature of operating gas, power, frequency, temperature). For example, in the sonolysis of Ar-saturated terephthalate solutions at room temperature, a frequency of 321 kHz, and a power of 170 W kg-1, the total yield [G(.OH) + 2 G(H2O2)], equals 16 x 10(-10) mol J-1. This represents the total of .OH that reach the liquid phase from gas phase of the cavitating bubble. The higher the solute concentration, the lower the H2O2 production as more of the OH free radicals are scavenged, in competition with their recombination. Fricke dosimetry, in the absence and presence of Cu2+ ions, shows that the yield of H atom reaching the liquid phase is much lower, with G(H.) of the order of 3 x 10(-10) mol J-1. These sonolytic yields are smaller in solutions that are at the point of gas saturation, and increase to an optimum as the initial sonication-induced degassing and effervescence subsides. The probing of the sonic field has shown that the rate of sonolytic free-radical formation may vary across the sonicated volume depending on frequency and power input.

Journal Article↗
PubMed1998

Characterization of recombinant hepatitis B surface antigen using surface plasmon resonance.

Two commercial monoclonal antibodies were shown to interact with distinct epitopes within the major antigenic a determinant region of yeast recombinant hepatitis B surface antigen (rHBsAg) particles, contained in the hepatitis B vaccine, by using the surface plasmon resonance phenomenon on a BIAcore system. Apparent avidity for these antibodies were compared among different rHBsAg batches, showing the consistency of these epitopes. Furthermore, the effect of the alteration of these epitopes, achieved by chemical modifications, was readily reflected by changes in the apparent avidity for these antibodies. The procedures used in the present study provide a novel and efficient way to characterize rHBsAg particles present in different hepatitis B vaccine products.

Antibodies, Monoclonal↗
PubMed1998

[Granulomatous tumor of the flexor tendon sheath as first manifestation of sarcoidosis].

While osseous tumors of the phalanges are more common, soft-tissue manifestations in the hand are uncommon in patients with sarcoidosis. Our patient presented with a large but painless tumor on the palmar aspect of the right index finger limiting finger flexion. Histology of a biopsy specimen was interpreted as a granuloma of sarcoidosis. Further X-ray investigations revealed large bilateral formations in the hila of the lung interpreted as stage I sarcoidosis in an otherwise healthy individual. Tuberculosis and polyarthritis were excluded by standard tests. The tumor was then radically excised, as it was located within the flexor tendon sheath. After uneventful wound healing the patient had regained full function of his finger at six weeks follow up. Interestingly enough, a chest film at that time showed the hilar changes to have decreased as well, which is considered quite typical for this disease.

Adult↗
PubMed1996

Affinity maturation of a high-affinity human monoclonal antibody against the third hypervariable loop of human immunodeficiency virus: use of phage display to improve affinity and broaden strain reactivity.

The present study set out to investigate whether phage display could be used to improve the properties of a high-affinity human monoclonal antibody directed against the third hypervariable loop (V3 loop) of human immunodeficiency virus (HIV). The aim was to increase affinity through slowing the dissociation rate (off-rate constant of koff), whilst retaining the ability of this antibody to bind diverse V3 loop sequences. When reformatted as a scFv, the antibody fragment retained the properties of the parental IgG, including the ability to neutralise virus. Heavy and light chains were sequentially replaced with repertoires of variable domains from non-immunised human donors followed by selection on biotinylated synthetic peptide. All selected variants derived from the same germline as the parental antibody. Variants of the light chain provided little if any improvement, whereas two residue changes in VHCDR2 and one in VHFR3 resulted in a reduced koff from gp120 protein of the MN strain (MNgp120) and synthetic V3 loop peptides as measured by surface plasmon resonance using the BIAcore instrument (Pharmacia Biosensor). VHCDR3 was modified using synthetic oligonucleotides and several clones with reduced koff identified, a number of different substitutions occurring at a single residue position. The residues in the heavy chain identified as reducing koff were simultaneously randomised by site-directed mutagenesis, resulting in scFv variants with koff slowed up to sevenfold. Far from compromising recognition of variant loops, binding to these sequences was improved; the koff from synthetic peptides modelled on V3 loop variants being slowed to a degree similar to that observed with MNgp120. All four changes were located towards either extremes of CDRs 2 and 3, suggesting that the mechanism of improvement may be one of alternation of loop conformation. This work illustrates that phage display can be used to tailor the properties of a therapeutic monoclonal antibody in a predefined fashion.

Amino Acid Sequence↗
PubMed1996

[Trigger thumb in the child].

The trigger thumb is a quite frequent finding in the adult woman over 50 years. In newly born and small children we do, however, also occasionally observe trigger thumbs. As even pediatric specialists are not necessarily familiar with this diagnosis, they tend to refer these small patients as emergencies for acute distortions or subluxations. We describe the clinical findings and therapy for trigger thumb in the child and our own results in comparison with the literature. Except in the small child under six months, who displays a spontaneous recovery in about 30% of the cases, early surgical release of the pulley is the treatment of choice.

Adult↗
PubMed1995

[Smoking cessation at work exemplified by "action blanca casa", a project for smoking cessation in the D. Swarovski & Co., Wattens, firm].

Recent studies about the efficacy of smoking cessation programs in the workplace have brought up to common difficulties. Only long-term-programs show remarkable effects on smoking habits of the workers. Presenting ongoing long-term strategies for open discussion can improve the design of more powerful cessation programs in the future. Our program as an important part of modern "human resources management" is demonstrated and the results after 18 months are discussed.

Adult↗
PubMed1994

The influence of different amounts of n-3 polyunsaturated fatty acids on bleeding time and in vivo vascular reactivity.

Mesenteric bleeding time, mesenteric vascular reactivity, platelet and erythrocyte lipid fatty acid composition were measured at 2-3 weeks, 5-6 weeks and 11-22 weeks in normotensive Wistar rats, fed on high (6.5% energy) or moderate (1.6% energy) intakes of eicosapentaenoic acid (20:5n-3; EPA) as fish oil, compared with controls fed on a diet devoid of EPA. All diets contained the same level of linoleic acid (4% energy): the moderate- and high-EPA diets also contained 1.1 and 4.4% of the energy as docosahexaenoic acid (22:6n-3) respectively. Moderate, but not high, intakes of EPA increased mesenteric bleeding time. Similar reductions in erythrocyte and platelet arachidonic acid (20:4n-6) occurred in animals fed on either high or low amounts of EPA, but the proportion of EPA increased dose-dependently. At high intakes of EPA the proportion of oleic acid in platelets and erythrocytes was decreased. Blood pressure platelet counts, mesenteric vessel diameter and mesenteric vascular reactivity to vasopressin were unaffected by treatment. High intakes of fish oil led to a slight fall in packed cell volume. In a second experiment bleeding time and mesenteric vascular reactivity to noradrenaline were increased 2-4 weeks after receiving a moderate intake of EPA and these effects persisted 5-21 d after switching to a control diet. A similar increase in vascular reactivity to noradrenaline was observed in animals given indomethacin (6 mg/kg) but not in those given aspirin (20 mg/kg).

Animals↗
PubMed1993

Identification of multiple repeat sequences and transcription-related elements within introns 4, 8 and 9 of human Raf-1.

Oncogenic activation of the human c-raf-1 protein (Raf-1) occurs by truncation of its aminoterminus (regulatory domain) and retention of the carboxyterminus (kinase domain). To gain insight into the structure of human raf-1 genomic DNA corresponding to the regulatory domain of Raf-1, we analyzed the nucleotide sequences of introns 4, 8, and 9. Very high frequencies of the direct and indirect repeats, and A/T nucleotides were observed within introns 4, 8, and 9; and the DNA sequences, 5'-TTAGTCA-3' and 5'-TGATTCA-3', like the DNA recognition site of transcription factor AP-1, were identified within intron 4 of raf-1 in human normal and tumor DNAs. In addition, several transcriptional elements (CAAT box, TATA sequences, eukaryotic transcription initiation sites, and cellular transcriptional elements) were found within introns 4, 8, and 9 of human raf-1. These data suggest: 1) the high frequency of intron-specific repeats is a possible recombinational mechanism for derivation of truncated oncogenic forms of Raf-1; and 2) the multiple transcriptional elements within introns 4, 8, and 9 may have important implications in the regulation of raf-1 transcription and, therefore, its role in cell growth and proliferation.

Base Sequence↗
PubMed1993

[Distal radius fractures: conservative or surgical treatment?].

The "classical" Colles fracture of the distal radius is the most common fracture in the adult. In order to reduce the still rather high rate of permanent disability, this fracture involving a functionally important joint requires accurate reduction. The AO-fracture classification introduced by Müller not only defines the severity of an injury, but also allows for decision-making as to the most adequate treatment. Besides the purely conservative management by closed reduction and plaster cast for the type-A fractures, we have a number of other treatment modalities for the more complex-B and C-type fractures, such as closed reduction and percutaneous K-wire application or the use of the small external fixator as well as open reduction and internal fixation by plates and screws for a few selected indications.

Adolescent↗